Diagnostic assay systems in many cases involve the use of particles in a liquid to allow reactions to take place. These involve methods for detection of chemical binding reactions, for example in connection with antigens or antibodies. For correct conduct of assays using these systems, it is generally necessary for the particles in the associated containers to have the most homogeneous dispersion possible at the time of removal. A homogeneous particle dispersion avoids, for example, differences in concentration, caused by sedimentation processes, between successive withdrawals from the containers.
In the area of clinical diagnostic analysis systems for homogenization of particles, for example magnet particles, with connected particle-charged reagent containers, the following methods are already known. Rotary paddles are used. Such rotary paddles are known from EP 0 745 855 and from U.S. Pat. No. 6,772,962. Furthermore, use is made of intermittently rotating circular plastic vials which are equipped with radial inner fins, such as are known from U.S. Pat. No. 5,637,962, U.S. Pat. No. 5,795,784 or also from U.S. Pat. No. 5,856,194. In addition, ultrasound methods are known in which a metering needle excited by ultrasound plunges into the liquid and mixes the latter thoroughly. Such solutions can be taken for example from U.S. Pat. No. 5,658,799, EP 0 580 483 or from U.S. Pat. No. 5,985,672. It is also known to immerse a glass ball into a round, eccentrically rotating glass vial in order to force the content of the glass vial into a mixing movement. Such a method is known, for example, from U.S. Pat. No. 5,183,638. The prior art also includes reagent cartridges having a rotatably mounted container which is driven via a friction gear, for example from U.S. Pat. No. 5,580,524 or from EP 0 435 481.
The methods known from the prior art for homogenizing particle-charged reagents, for example in analysis systems using external actuators such as paddles, have a number of disadvantages. Such a method for homogenization of particle-charged reagents constitutes an invasive mixing method. This means that in principle there is a risk of entrainment between different particle-charged reagent containers. To counteract the risk of entrainment in such analysis systems, these systems use special wash stations and wash fluids with which the risk of entrainment is intended to be counteracted. However, this involves a much greater outlay in terms of equipment in such analysis systems. In analysis systems which use external actuators, for example paddles, for homogenization of particle-charged reagents, a plurality of reagent containers can be processed only sequentially. This in turn means long preparation times for an operation, and there are limitations on the configuration of the apparatus cycle, the time for access to other reagent containers, and the apparatus cycle time. Particle-charged reagents homogenized according to these methods show increased foam formation as the volume of liquid decreases, which results in relatively high reagent pressure volumes.
In certain types of particles, invasively operating ultrasound systems lead to inadmissible changes in the particle coating. A similar phenomenon occurs upon invasive addition of auxiliaries, as represented for example by glass balls. In systems in which radial internal fins are used for homogenization of particle-charged reagents, considerable foam formation takes place when certain liquids are mixed together; the liquid also sprays, which is highly unsatisfactory.
In the systems which are known from the prior art according to U.S. Pat. No. 5,788,928 and EP 0 757 253 and use pivotable cartridges, a significantly greater container volume is generally needed, resulting in more space being required for such systems.
In view of the disadvantages of the methods known from the prior art for homogenization of particle-charged reagents, the object of the present invention is to permit homogenization of particle-charged reagents non-invasively by rotation of a container.
According to the invention, this object is achieved by the features of the claimed invention.
The advantages of the solution proposed according to the invention are that the risk of entrainment can be definitively ruled out by the proposed non-invasive homogenization of the particle-charged liquid. No wash stations are needed. Moreover, no wash fluid is needed, and, finally, no liquid waste is obtained which then has to be disposed of in compliance with legal requirements. In addition, an extremely low dead volume can be achieved, as a result of which the reagent can be better utilized, since foam formation, of the kind arising in the methods known from the prior art, is suppressed. The solution proposed according to the invention also permits greater degrees of freedom in system configuration and affords the possibility of parallelization of access in the reagent area since, from several containers containing reagents, access can be made to one container unit. The parallelization further permits considerably shorter processing times for homogenization, compared to sequential processing.
Moreover, the solution proposed according to the invention permits a parallelization of the first homogenization for reagent cartridges; because of possible particle sedimentation, the first homogenization can in fact be especially time-consuming. Before the first homogenization, no liquid level detection is required, because, when mixing by means of vial rotation, the liquid level inside the reagent cartridges does not need to be known. In contrast, this is required in mixing processes using stirrer paddles, since insufficient immersion of the stirrer paddles can lead to foam formation and undesired spraying.
The assemblable cartridge proposed according to the invention also affords the advantage that lid opening and lid closure operations are no longer needed in the homogenization. The reagent cartridge proposed according to the invention and receiving several reagents is provided with a film closure which avoids extra cycles, such as opening and closing, and thus reduces the throughput times.
The assemblable reagent cartridge proposed according to the invention further represents a cost-effective plastic component which can be mass-produced and permits straightforward cartridge assembly. Thus, a cartridge can be assembled by means of two clip parts provided with curvatures being simply fitted together so as to enclose a container holding particle-charged reagents. The connectable clip parts have large flat surfaces which considerably facilitate labelling. The individual clip parts and the container receiving the particle-charged liquid can be filled at different times from one another.